Retinoid X Receptor Gamma Control of Affective Behaviors Involves Dopaminergic Signaling in Mice

Krzyżosiak, Agnieszka; Szyszka-Niagolov, Monika; Wietrzych, Marta; Gobaille, Serge; Muramatsu, Shin‐ichi; Krężel, Wojciech

doi:10.1016/j.neuron.2010.05.004

Cited by 67 publications

(73 citation statements)

References 46 publications

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“…Importantly, Rxrg -/-mice show increased despair behaviour and another key symptom of depression (anhedonia), which are both reversed by chronic antidepressant treatment. Adenovirus-mediated re-expression of RXR within the NAc also reversed these behaviours, clearly demonstrating a postnatal function for RXR signalling (Krzyzosiak et al, 2010). These findings suggest that altered retinoid signalling could contribute to diseases affecting the nigrostriatal system, such as Parkinson's and Huntington's diseases.…”

Section: Ra Function During Somitogenesis and Neural Tube Differentiamentioning

confidence: 72%

Retinoic acid signalling during development

2012

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Retinoic acid (RA) is a vitamin A-derived, non-peptidic, small lipophilic molecule that acts as ligand for nuclear RA receptors (RARs), converting them from transcriptional repressors to activators. The distribution and levels of RA in embryonic tissues are tightly controlled by regulated synthesis through the action of specific retinol and retinaldehyde dehydrogenases and by degradation via specific cytochrome P450s (CYP26s). Recent studies indicate that RA action involves an interplay between diffusion (morphogen-like) gradients and the establishment of signalling boundaries due to RA metabolism, thereby allowing RA to finely control the differentiation and patterning of various stem/progenitor cell populations. Here, we provide an overview of the RA biosynthesis, degradation and signalling pathways and review the main functions of this molecule during embryogenesis.

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Section: Ra Function During Somitogenesis and Neural Tube Differentiamentioning

confidence: 72%

Retinoic acid signalling during development

2012

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“…LGE samples (n ϭ 5 WT and 5 Rarb Ϫ/Ϫ for each stage) and normalized for expression of a housekeeping gene 36B4 as previously described (Krzyzosiak et al, 2010). PCRs were performed in duplicate or triplicate with good reproducibility rate (error, Ͻ10%).…”

Section: Methodsmentioning

confidence: 99%

Retinoic Acid Receptor β Controls Development of Striatonigral Projection Neurons through FGF-Dependent and Meis1-Dependent Mechanisms

Rataj-Baniowska¹,

Niewiadomska-Cimicka²,

Paschaki³

et al. 2015

J. Neurosci.

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The mammalian striatum controls sensorimotor and psychoaffective functions through coordinated activities of its two striatonigral and striatopallidal output pathways. Here we show that retinoic acid receptor ␤ (RAR␤) controls development of a subpopulation of GABAergic, Gad65-positive striatonigral projection neurons. In Rarb Ϫ/Ϫ knock-out mice, concomitant reduction of Gad65, dopamine receptor D1 (Drd1), and substance P expression at different phases of prenatal development was associated with reduced number of Drd1-positive cells at birth, in contrast to normal numbers of striatopallidal projection neurons expressing dopamine receptor D2.

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“…4). Finally, RA signaling has been implicated in the regulation of affective behaviors and findings from a specific retinoid receptor knockout mouse model suggest that RA signaling is required for fluoxetine's antidepressant actions (Krzyzosiak et al 2010;Bremner et al 2012;Wietrzych-Schindler et al 2011). Neuronal RA signaling is believed to be the result of a homeostatic balance between local RA synthesis and, more importantly, its feedbackregulated, cytochrome P450-(CYP450) mediated degradation (Shimozono et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Direct inhibition of retinoic acid catabolism by fluoxetine

et al. 2015

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Recent evidence from animal and human studies suggests neuroprotective effects of the SSRI fluoxetine, e.g., in the aftermath of stroke. The underlying molecular mechanisms remain to be fully defined. Because of its effects on the cytochrome P450 system (CYP450), we hypothesized that neuroprotection by fluoxetine is related to altered metabolism of retinoic acid (RA), whose CYP450-mediated degradation in brain tissue constitutes an important step in the regulation of its site-specific auto- and paracrine actions. Using traditional pharmacological in vitro assays, the effects of fluoxetine on RA degradation were probed in crude synaptosomes from rat brain and human-derived SH-SY5Y cells, and in cultures of neuron-like SH-SY5Y cells. Furthermore, retinoid-dependent effects of fluoxetine on neuronal survival following glutamate exposure were investigated in rat primary neurons cells using specific retinoid receptor antagonists. Experiments revealed dose-dependent inhibition of synaptosomal RA degradation by fluoxetine along with dose-dependent increases in RA levels in cell cultures. Furthermore, fluoxetine's neuroprotective effects against glutamate excitotoxicity in rat primary neurons were demonstrated to partially depend on RA signaling. Taken together, these findings demonstrate for the first time that the potent, pleiotropic antidepressant fluoxetine directly interacts with RA homeostasis in brain tissue, thereby exerting its neuroprotective effects.

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Retinoid X Receptor Gamma Control of Affective Behaviors Involves Dopaminergic Signaling in Mice

Cited by 67 publications

References 46 publications

Retinoic acid signalling during development

Retinoic acid signalling during development

Retinoic Acid Receptor β Controls Development of Striatonigral Projection Neurons through FGF-Dependent and Meis1-Dependent Mechanisms

Direct inhibition of retinoic acid catabolism by fluoxetine

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